关键词: DNA methylation MS-HRM biomarker gliomas

Mesh : Adolescent Adult Aged Aged, 80 and over Biomarkers, Tumor / genetics metabolism Brain Neoplasms / genetics metabolism DNA Methylation / physiology Female Glioma / genetics metabolism Humans Male Middle Aged Promoter Regions, Genetic / physiology Young Adult

来  源:   DOI:10.1111/cns.13443   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Local DNA hypermethylation is a potential source of cancer biomarkers. While the evaluation of single gene methylation has limited value, their selected panel may provide better information.
This study aimed to analyze the promoter methylation level in a 7-gene panel in brain tumors and verifies the usefulness of methylation-sensitive high-resolution melting (MS-HRM) for this purpose.
Forty-six glioma samples and one non-neoplastic brain sample were analyzed by MS-HRM in terms of SFRP1, SFRP2, RUNX3, CBLN4, INA, MGMT, and RASSF1A promoter methylation. The results were correlated with patients\' clinicopathological features.
DNA methylation level of all analyzed genes was significantly higher in brain tumor samples as compared to non-neoplastic brain and commercial, unmethylated DNA control. RASSF1A was the most frequently methylated gene, with statistically significant differences depending on the tumor WHO grade. Higher MGMT methylation levels were observed in females, whereas the levels of SFRP1 and INA promoter methylation significantly increased with patients\' age. A positive correlation of promoter methylation levels was observed between pairs of genes, for example, CBLN4 and INA or MGMT and RASSF1A.
Our 7-gene panel of promoter methylation can be helpful in brain tumor diagnosis or characterization, and MS-HRM is a suitable method for its analysis.
摘要:
局部DNA超甲基化是癌症生物标志物的潜在来源。虽然单基因甲基化的评价价值有限,他们选择的小组可能会提供更好的信息。
本研究旨在分析脑肿瘤中7个基因组中的启动子甲基化水平,并验证甲基化敏感性高分辨率熔解(MS-HRM)用于此目的的有用性。
通过MS-HRM根据SFRP1,SFRP2,RUNX3,CBLN4,INA,分析了46个神经胶质瘤样本和一个非肿瘤性脑样本。MGMT,和RASSF1A启动子甲基化。结果与患者的临床病理特征相关。
所有分析基因的DNA甲基化水平在脑肿瘤样本中显著高于非肿瘤性脑和商业,未甲基化的DNA对照。RASSF1A是最常见的甲基化基因,根据肿瘤的WHO等级,具有统计学上的显着差异。在女性中观察到较高的MGMT甲基化水平,而SFRP1和INA启动子甲基化水平随患者年龄显著增加。在一对基因之间观察到启动子甲基化水平呈正相关,例如,CBLN4和INA或MGMT和RASSF1A。
我们的7个基因组的启动子甲基化可能有助于脑肿瘤的诊断或表征,MS-HRM是一种合适的分析方法。
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